A stroke, also known as a “brain attack,” cerebrovascular accident (CVA) or acute ischemic cerebrovascular syndrome, is a loss of brain function(s), usually rapidly developing, that is due to a disturbance in the blood vessels supplying blood to the brain or brainstem. The disturbance can be ischemia (lack of blood) caused by, e.g., thrombosis or embolism, or can be due to a hemorrhage. According to the World Health Organization, stroke is a “neurological deficit of cerebrovascular cause that persists beyond 24 hours or is interrupted by death within 24 hours.” Persistence of symptoms beyond 24 hours separates stroke from Transient Ischemic Attack (TIA), in which symptoms persist for less than 24 hours.
Currently, treatment of ischemic stroke typically includes antiplatelet medication such as aspirin, clopidogrel, dipyridamole, or anticoagulant medication, such as warfarin, to reduce or relieve blockage causing the ischemia. In addition, blood sugar levels are brought to as normal as possible, and the stroke patient is provided adequate oxygen and intravenous fluids. Treatment of hemorrhagic stroke generally comprises one or more of administration of a blood pressure-lowering drug, administration of a pain medication other than a non-steroidal anti-inflammatory drug (NSAID), administration of a calcium channel blocker (e.g., Nimodipine), and surgery, if indicated, to repair the vessel ruptures responsible for hemorrhage.
However, such treatments only attempt to mitigate ongoing neurological damage, and do nothing to restore lost function. Numerous non-cellular neuroprotective agents have been tested for efficacy in treatment of stroke, and have failed, including N-methyl-D-aspartate receptor antagonists, nalmefene, lubeluzole, clomethiazole, calcium channel blockers (including a-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid antagonists, serotonin agonists (e.g., repinotan), and transmembrane potassium channel modulators), tirilazad, anti-ICAM-1 antibody, human antileukocytic antibody (Hu23F2G), antiplatelet antibody (e.g., abciximab), citicoline (an exogenous form of cytidine-5′-diphosphocholine), and basic fibroblast growth factor.
There are no effective treatments for stroke. Thus, a need exists for therapies that not only mitigate neurological damage arising from either condition, but improve neural function and prognosis.